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Changes in Resting and Exercise Hemodynamics Early After Heart Transplantation: A Simulation Perspective.

ABSTRACT: Introduction: During heart transplantation (HTx), cardiac denervation is inevitable, thus typically resulting in chronic resting tachycardia and chronotropic incompetence with possible consequences in patient quality of life and clinical outcomes. To this date, knowledge of hemodynamic changes early after HTx is still incomplete. This study aims at providing a model-based description of the complex hemodynamic changes at rest and during exercise in HTx recipients (HTxRs). Materials and Methods: A numerical model of early HTxRs is developed that integrates intrinsic and autonomic heart rate (HR) control into a lumped-parameter cardiovascular system model. Intrinsic HR control is realized by a single-cell sinoatrial (SA) node model. Autonomic HR control is governed by aortic baroreflex and pulmonary stretch reflex and modulates SA node activity through neurotransmitter release. The model is tuned based on published clinical data of 15 studies. Simulations of rest and exercise are performed to study hemodynamic changes associated with HTxRs. Results: Simulations of HTxRs at rest predict a substantially increased HR [93.8 vs. 69.5 beats/min (bpm)] due to vagal denervation while maintaining normal cardiac output (CO) (5.2 vs. 5.6 L/min) through a reduction in stroke volume (SV) (55.4 vs. 82 mL). Simulations of exercise predict markedly reduced peak CO (13 vs. 19.8 L/min) primarily resulting from diminished peak HRs (133.9 vs. 169 bpm) and reduced ventricular contractility. Yet, the model results show that HTxRs can maintain normal CO for low- to medium-intensity exercise by increased SV augmentation through the Frank-Starling mechanism. Conclusion: Relevant hemodynamic changes occur after HTx. Simulations suggest that (1) increased resting HRs solely result from the absence of vagal tone; (2) chronotropic incompetence is the main limiting factor of exercise capacity whereby peripheral factors play a secondary role; and (3) despite the diminished exercise capacity, HTxRs can compensate chronotropic incompetence by a preload-mediated increase in SV augmentation and thus maintain normal CO in low- to medium-intensity exercise.

SUBMITTER: Haberbusch M

PROVIDER: S-EPMC7677526 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Changes in Resting and Exercise Hemodynamics Early After Heart Transplantation: A Simulation Perspective.

Haberbusch Max M De Luca Daniela D Moscato Francesco F

Frontiers in physiology 20201106

<b>Introduction:</b> During heart transplantation (HTx), cardiac denervation is inevitable, thus typically resulting in chronic resting tachycardia and chronotropic incompetence with possible consequences in patient quality of life and clinical outcomes. To this date, knowledge of hemodynamic changes early after HTx is still incomplete. This study aims at providing a model-based description of the complex hemodynamic changes at rest and during exercise in HTx recipients (HTxRs). <b>Materials and ...[more]

PMID: 33240102

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Project description:AimsMaximal exercise capacity as measured by peak oxygen consumption (pVO2 ) in cardiopulmonary exercise testing (CPET) of heart transplant recipients (HTR) is limited to a 50-70% level of healthy age-matched controls. This study investigated the relationship between body composition and pVO2 during the first decade post-transplant.Methods and resultsBody composition was determined by dual-energy X-ray absorptiometry (DXA) and pVO2 by CPET in 48 HTR (n = 38 males; mean age 51 ± 12 years). A total of 95 assessments were acquired 1-9 years post-transplant, and the results of four consecutive periods were compared [Period 1: 1-2 years (n = 25); 2: 3-4 years (n = 23); 3: 5-6 years (n = 23); 4: 7-9 years (n = 24)]. Linear regression analysis analysed the correlation between pVO2 and pairs of appendicular lean mass (ALM) and fat mass (FM). The relation between ALM and daily dose of calcineurin inhibitor (CNI) was explored using partial correlation controlling for age, gender, and height. pVO2 increased from 0.98 (0.34) to 1.35 (0.35) L/min (P < 0.01) between Periods 1 and 4 corresponding to 54.5-63.3% of predicted value. Peak heart rate (HR) raised from 115 ± 19 to 131 ± 23 b.p.m. (P = 0.05), and anaerobic threshold (AT = VO2 achieved at AT) increased from 0.57 (0.18) to 0.83 (0.35) L/min (P < 0.01) between Periods 1 and 3. Median FM normalized to height2 (FMI) always remained elevated (>8.8 kg/m2 ). ALM normalized to body mass index increased from 0.690 (0.188) to 0.848 (0.204) m2 (P = 0.02) between Periods 1 and 4, explaining 45% of the variance of pVO2 (R2 = 0.455; P < 0.001). Eighty-one per cent of the variance of pVO2 (R2 = 0.817; P < 0.001) in multiple regression was explained by AT (β = 0.488), ALM (β = 0.396), peak HR (β = 0.366), and FMI (β = -0.181). ALM was negatively correlated with daily CNI dose (partial R = -0.258; P = 0.01).ConclusionsAfter heart transplantation, the beneficial effect of peripheral skeletal muscle gain on pVO2 is opposed by increased FM. Our findings support lifestyle efforts to fight adiposity and CNI dose reduction in the chronic stable phase to favour positive adaptation of peripheral muscle mass.

Project description:AimsWe aim to evaluate changes in invasive haemodynamics, right ventricular (RV) function, and perfusion during the first year after heart transplantation (HTx) and to determine the relation between RV function and myocardial perfusion.Methods and resultsThirty patients were prospectively enrolled at the time of HTx. Right heart catheterization (RHC), comprehensive 2D and 3D echocardiography and cardiac biomarkers were performed at baseline (≤2 weeks after HTx) and at follow-up 1, 3, 6, and 12 months after HTx. At 12 months, HTx patients were subjected to an exercise stress test with assessment of maximal oxygen consumption (VO2 max). RV myocardial perfusion reserve was evaluated by 15 O-H2 O positron emission tomography at baseline and at 3 and 12 months after HTx. A group of 43 healthy subjects served as echocardiographic controls and a subgroup comprising 16 healthy controls underwent exercise stress test with simultaneous RHC. At baseline, HTx patients had higher pulmonary artery wedge pressure (PAWP) and right atrial pressure (RAP) and pulmonary vascular resistance (PVR) than healthy controls whereas cardiac index (CI) was reduced (PAWP; 14 mmHg [8;17] vs. 8 mmHg [7;10]; RAP: 7 mmHg [4;11] vs. 5 mmHg [4;6]; PVR: 1.9 wood units [1.3;2.6] vs. 1.1 wood units [1.0;1.4]; CI 2.4 L/min/m2 [2.2;2.8] vs. 3.3 L/min/m2 [2.8;.3.6], all P < 0.05). Normalization of filling pressures and CI was seen 3-6 months after HTx. During follow-up, RV function in terms of 3D ejection fraction (EF) and longitudinal strain (LS) improved in HTx patients but remained reduced compared with healthy controls at 12 months follow-up (3D RV EF: 52 ± 7% vs. 60 ± 8%; RV LS: 22 ± 4% vs. 28 ± 5%, both P < 0.001). During follow-up, RV perfusion reserve improved (baseline 2.1 ± 0.9; 3 months follow-up 3.2 ± 0.8; 12 months follow-up 3.7 ± 1.1, P < 0.0001). RV perfusion reserve significantly correlated to cardiac markers in terms of troponin T (r = -0.62, P < 0.0001), NT-proBNP (r = -0.65, P < 0.0001), RAP (r = -0.43, P < 0.01) and CI (r = 0.37, P < 0.01) and with VO2 max 12 months after HTx (r = 0.75, P < 0.01).ConclusionsNormalization of left and right atrial filling pressures is demonstrated within the first 3 to 6 months after HTx. RV function and RV perfusion reserve correlated and gradually improved during the first year after HTx but RV function remained reduced in HTx patients compared with healthy controls.

Project description:RationaleAbnormalities in nitric oxide signaling play a pivotal role in heart failure with preserved ejection fraction (HFpEF). Intravenous sodium nitrite, which is converted to nitric oxide in vivo, improves hemodynamics in HFpEF, but its use is limited by the need for parenteral administration. Nitrite can also be administered using a novel, portable micronebulizer system suitable for chronic use.ObjectiveDetermine whether inhaled nitrite improves hemodynamics in HFpEF.Methods and resultsIn a double-blind, randomized, placebo-controlled, parallel-group trial, subjects with HFpEF (n=26) underwent cardiac catheterization with simultaneous expired gas analysis at rest and during exercise before and after treatment with inhaled sodium nitrite (90 mg) or placebo. The primary end point was the pulmonary capillary wedge pressure during exercise. Before study drug administration, HFpEF subjects displayed an increase in pulmonary capillary wedge pressure with exercise from 20±6 to 34±7 mm Hg (P<0.0001). After study drug administration, exercise pulmonary capillary wedge pressure was substantially improved by nitrite as compared with placebo (baseline-adjusted mean 25±5 versus 31±6 mm Hg; analysis of covariance P=0.022). Inhaled nitrite reduced resting pulmonary capillary wedge pressure (-4±3 versus -1±2 mm Hg; P=0.002), improved pulmonary artery compliance (+1.5±1.1 versus +0.6±0.9 mL/mm Hg), and decreased mean pulmonary artery pressures at rest (-7±4 versus -3±4 mm Hg; P=0.007) and with exercise (-10±6 versus -5±6 mm Hg; P=0.05). Nitrite reduced right atrial pressures, with no effect on cardiac output or stroke volume.ConclusionsAcute administration of inhaled sodium nitrite reduces biventricular filling pressures and pulmonary artery pressures at rest and during exercise in HFpEF. Further study is warranted to evaluate chronic effects of inhaled nitrite in HFpEF.Clinical trial registrationThis single center randomized clinical trial is registered at clinicaltrials.gov (NCT02262078).

Dataset Information

Changes in Resting and Exercise Hemodynamics Early After Heart Transplantation: A Simulation Perspective.

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Changes in Resting and Exercise Hemodynamics Early After Heart Transplantation: A Simulation Perspective.

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